THE J-C INTRON: A MUTATION INDICATOR IN BOVINE V GENES

描述（改编自申请人的摘要）：重排和体细胞 突变有助于牛的一抗库多样化。 非模板体细胞突变，基因转换，或两者的组合， 被认为是牛科中剧目多样化的主要发生器。 然而，牛和牛中重链和轻链V基因的大部分组成， 羊是未知的。因此，很难确切地确定， 表达的抗体基因中的特定变异是否是由于突变 或重排。基因转换也很难区分 和无模板的体细胞点突变拟议的研究需要进行实验 将利用J-C内含子序列的变异来解决这些问题。的 具体目标如下：1）使用J-C内含子作为诊断 牛λ轻链中使用的突变机制的指示剂 多样化经营。2)牛重链J-C内含子作为中性内含子的用途 牛重链突变多样化指标。3)使用J-C 内含子作为牛突变机制的诊断指标 重链突变多样化。J-C内含子的检查提供了 它既是突变的中性指标，也是区分基因 转化（模板突变）和体细胞突变（非模板突变）。 轻链和重链J-C内含子的表征和 它们作为"突变计"的效用， 牛抗体基因的突变将建立一个有用的工具， 牛IG基因变异。申请人建议，这种方法可以 为进一步研究牛体细胞突变提供了一种简便的方法 免疫球蛋白基因在器官和细胞培养中的作用。

DESCRIPTION (Adapted from the Applicant's Abstract): Rearrangement and somatic mutation contribute to primary antibody repertoire diversification in cattle. Untemplated somatic mutation, gene conversion, or a combination of both, is thought to be the major generator of repertoire diversification in the Bovidae. However, much of the repertoire of heavy and light chain V genes in cattle and sheep remains unknown. Thus, it is difficult to determine, definitively, whether particular variations in expressed antibody genes are due to mutation or rearrangement. It is also difficult to discriminate between gene conversion and untemplated somatic point mutation. The proposed studies entail experiments that will use variation in J-C intron sequences to resolve these issues. The following specific aims were listed: 1) Use of the J-C intron as a diagnostic indicator of the mutational mechanisms used in bovine lambda light chain diversification. 2) Use of the bovine heavy chain J-C intron as a neutral indicator of bovine heavy chain mutational diversification. 3) Use of the J-C intron as a diagnostic indicator of the mutational mechanism employed in bovine heavy chain mutational diversification. Examination of the J-C intron provides both a neutral indicator of mutation and a way a to discriminate between gene conversion (templated mutation) and somatic mutation (untemplated mutation). Characterization of light and heavy chain J-C introns and demonstration of their utility as "mutometers" for detecting the occurrence and mechanism of mutation in bovine antibody genes will establish a useful tool for analysis of variation in bovine Ig genes. The applicant proposes that this approach may provide a convenient assay for future study of somatic mutation of bovine immunoglobulin genes in organ and cell culture.